- Email: [email protected]
Magnetic resonance spectroscopy: a noninvasive diagnosis of gliomatosis cerebri
Magnetic Resonance Imaging 24 (2006) 205 – 207
Magnetic resonance spectroscopy: a noninvasive diagnosis of gliomatosis cerebri Evangelia Kararizou a,*, Dimitrios Likomanosb, Konstantinos Gkiatasb, Ioannis Markoub, Nikolaos Triantafylloua, Grhgorios Kararizosb a
Department of Neurology, Eginition Hospital, Athens National University, Athens, Greece PC 11525 b Neurological Clinic, Air Force Hospital, Athens, Greece PC 11525 Received 24 September 2005; revised 15 October 2005; accepted 15 October 2005
Abstract Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of neoplastic glial cells with preservation of neuronal architecture. It can be very difficult to diagnose during life because the clinical manifestations are protean and tests are often nondiagnostic. The diagnosis of GC needs to be based on radiological, clinical and pathological criteria. We present a patient with GC, which initially presented as acute stroke attack. We discuss the usefulness of noninvasive methods, such a MR spectroscopy, in the diagnosis, grading and management of GC. D 2006 Elsevier Inc. All rights reserved. Keywords: Gliomatosis cerebri; Magnetic resonance spectroscopy
1. Introduction Gliomatosis cerebri (GC) is a rare primary brain tumor of unknown origin characterized by the proliferation of neoplastic glial cells, and this process may involve multiple brain regions [1– 4]. It can be very difficult to diagnose during life because the clinical manifestations are protean and tests are often nondiagnostic [5,6]. The diagnosis of GC needs to be based on radiological, clinical and pathological criteria [7,8]. Magnetic resonance imaging (MRI) has become the radiological method of choice in the diagnosis of GC [9]. Conventional MRI shows a diffuse signal intensity abnormality in T2-weighted and fluid-attenuated inversion recovery images with minimal or no mass effect and a lack of contrast enhancement. Magnetic resonance spectroscopy (MRS), which may be added to conventional MRI exam, provides a noninvasive biochemical assay of normal and pathological brain tissue and may help narrow the differential diagnosis in favor of a neoplastic lesion by revealing increased Cho/Cr and Cho/NA and variably decreased NA/Cr [10,11]. We present a patient with GC, which initially presented as acute stroke attack. We discuss the usefulness of 4 Corresponding author. Neurologic Clinic, Aeginition Hospital, 11528 Athens, Greece. Tel.: +30 210 7289216; fax: +30 210 7250410. E-mail address: [email protected] (E. Kararizou ). 0730-725X/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.mri.2005.10.032
noninvasive methods, such MR spectroscopy, in the diagnosis, grading and management of GC. 2. Case report A 59-year-old female patient presented with acute onset of dizziness, nausea, confusion and olfactory hallucinations. She had a history of pulmonary embolism and had been treated with anticoagulant drugs. There were no complaints of cognitive or behavioral impairments. The clinical examination revealed decreased level of consciousness and confusion. The motor strength was normal, and no sensory deficits were detected. Babinski sign was negative. With these findings and the acute onset of symptoms, the diagnosis of stroke attack was made in another institution. Afterwards, the patient was admitted in Air Force Hospital, and, immediately, a head CT scan was performed, which revealed a heterogeneous lesion in the left frontal lobe, compressing the frontal horn of the left lateral ventricle and causing significant midline shift. Indefinite components of subarachnoid hemorrhage were also observed. Cranial MRI demonstrated extensive parenchymatous lesions with the following features: (a) extensive signal changes in the left cerebral hemisphere, especially involving the white matter of the temporal lobe with a frontoparietal spreading, including basal ganglia and internal
206
E. Kararizou et al. / Magnetic Resonance Imaging 24 (2006) 205 – 207
Fig. 1. Concentrations of the spectroscopic metabolites.
capsule. (b) T2-signal abnormalities in the white matter of the right hemicerebrum, especially occitotemporally via the corpus callosum. (c) An ischemic lesion was observed in the left occitotemporal district with peripheral hemorrhagic elements. (d) Other ischemic lesions were recognised in the left side of the midbrain and in the right side of pons. (e) Cerebral edema was extended up to the cortex of the left hemisphere, where cortical sulcuses were obscured. Magnetic resonance spectroscopy of the cerebral vasculature revealed no stenosis or occlusion of either carotid or vertebrobasilar circulation. From the imaging findings (head CT scan, cranial MRI) the differential diagnosis included GC, subacute encephalitis and any systemic disease with involvement of the central nervous system. So further laboratory examinations, including extended serologic tests for systemic infectious and inflammatory diseases, connective tissue and autoimmune diseases along with cancer, were performed and the results were all normal. Interictal EEG showed high-voltage activity with a left hemispheric predominance. As mentioned above, there was a history of pulmonary embolism and treatment with anticoagulants and this was the main reason that a brain biopsy was contraindicated. Proton MRS was performed. Four NMR spectra of protons with TE = 35 and 135 ms were taken from the lesion in the left temporoparietal area and the respective area of the right hemisphere (Fig. 1). The concentration of choline (Cho), N-acetyl-aspartate (NAA), creatine (Cr), myo-inositol (MI), lactate, lipids as well as the metabolic ratios of Cho/Cr, NAA/Cr and NAA/Cho was calculated (Table 1). The concentration of Cho in the lesion is 45% higher than that of the respective healthy region of cerebral hemisphere. This finding is compatible with neoplasm (or malignancy).
The NAA concentration is quite low in the lesion area (about 65%). The presence of Cr in the lesion area indicates neoplasm of diffuse type (glioma), and the elevation of the Cho/Cr is compatible with low-grade glioma. Finally, the presence of lactic acid indicates the initiation of alteration in parts of the lesion (anaplastic astrocytoma grade III). Taking into account the neuroimaging findings (extension of the lesion to the right hemisphere, heterogeneous contrast enhancement), we found that this lesion fulfills the criteria of WHO for being characterized as GC [12]. At that time the patient had been treated with corticosteroids that resulted in significant improvement of symptoms over a period of 3 months. Although the initial symptoms of our patient included dizziness, nausea, confusion and olfactory hallucinations, no neurological sign or symptom was reported or revealed during hospitalization, despite the extent of the cerebral lesion. The last MRI, which was performed in May 2005, was reported to be unchanged. The neurological examination did not reveal any pathological findings. 3. Discussion Gliomatosis cerebri is characterized by a diffuse infiltration of neoplastic glial cells with preservation of neuronal architecture. It was first described in a case report by Nevin [13] in 1938 as a glial neoplasm with diffuse infiltration throughout the brain yet with relative preservation of underlying neuronal architecture. In the latest WHO classification GC is listed as a subgroup of neuroepithelial tumors of uncertain origin with involvement of at least two lobes without a cellular, centrally necrotic center [12].
Table 1 Area
Cho (mM/kg)
Cr (mM/kg)
NAA (mM/kg)
MI (mM/kg)
NAA/Cr
Cho/Cr
MI/Cr
Lesion 1 Lesion 2 Healthy region
3.21 3.41 2.36
6.14 6.61 7.40
3.11 3.12 8.88
6.28 6.46 7.21
0.58 0.54 1.37
1.38 1.36 0.84
0.62 0.59 0.59
E. Kararizou et al. / Magnetic Resonance Imaging 24 (2006) 205 – 207
The diagnosis of GC during life is problematic and needs to be based on radiological, clinical and pathological criteria. There are many reports of a delayed antemortem diagnosis of GC [5,6]. In our case, brain biopsy was contraindicated because of the treatment with anticoagulants. The diagnosis was based especially on the neuroimaging studies. A recent report suggests that noninvasive biochemical assay of normal and pathological brain tissue with MR spectroscopy may be helpful in diagnosing GC [10,11,14,15]. The typical MRI appearance of GC is a lesion that grows without distinct borders, diffusely infiltrating multiple brain regions. However, the changes in MR images are nonspecific and the differential diagnosis includes ischemia, multiple sclerosis, encephalitis, leukodystrophies and subacute sclerosing panencephalitis [9]. Serologic and radiology tests excluded all other conditions considered in the differential diagnosis. Magnetic resonance spectroscopy is able to distinguish between glial tumors and tumors of neuronal origin. A number of previous studies have reported elevated Cho and decreased NAA and Cr, and this spectroscopic pattern of neoplastic brain lesions has been used to differentiate and to establish prognostic parameters [10,11,14,15]. The extent of Cho/Cr and Cho/NAA increases is of great importance in the grading of gliomatosis. According to the study of Fountas et al. [16], Cho/Pcr-Cr is a very important marker determining the degree of malignancy. Magnetic resonance spectroscopy can also be used for follow-up examination. The clinical manifestations of GC are usually progressive and nonspecific, and the acute onset as stroke is rare [1– 4]. With the use of radiation therapy and chemotherapy, survival is about 5% and the natural course is quite variable, with a duration between 25 days and 22 years [17,18]. Although the initial symptoms of our patient included dizziness, nausea, confusion and olfactory hallucinations, no neurological sign or symptom was reported or revealed during hospitalization, despite the extent of the cerebral lesion. In conclusion, our report suggests that MRS is a useful noninvasive method not only for diagnosis but also for grading and prognosis of GC and especially when there are contraindications for the biopsy study.
207
References [1] Scheinker IM, Evans JP. Diffuse cerebral glio-blastosis. J Neuropathol Exp Neurol 1943;2:178 – 89. [2] Intracranial neoplasms and paraneoplastic disorders. In: Adams RD, et al, editors. Principles of neurology, 8th ed. New York7 McGrawHill; 2000. p. 673 – 733. [3] Heffner RR. Pathology of nervous system tumors. In: Bradley WC, Daroff RB, Fenichel GM, Marsden CD, editors. Neurology in clinical practice. Boston7 Butterworth-Heinemann; 1995. p. 1091 – 108. [4] Akimodo J, Nishioka H, Miki T, Haraoka J, Kado M. Clinical diagnosis of gliomatosis cerebri: report of three cases. Brain Tumor Pathol 2004;21:87 – 95. [5] Phtinen J, P77kkf E. A difficult diagnosis of gliomatosis cerebri. Neuroradiology 1996;38:444 – 8. [6] Nishioka H, Ito H, Miki T. Difficulties in the antemortem diagnosis of gliomatosis cerebri: report of a case with diffuse increase of gemistocyte-like cells, mimicking reactive gliosis. Br J Neurosurg 1996;10:103 – 7. [7] Felsberg GJ, Silver SA, Brown MT, Tien RD. Gliomatosis cerebri: radiologic–pathologic correlation. Am J Neuroradiol 1994;15: 1745 – 51. [8] Caprio-O’Donovan R, Korah I, Salazar A, Melacon D. Gliomatosis cerebri. Radiology 1996;198:831 – 5. [9] Yang S, Wetzel S, Cha S. Dynamic contrast-enhanced T2*-weighted MR imaging of gliomatosis cerebri. Am J Neuroradiol 2002;23: 350 – 5. [10] Chang YW, Yoon HK, Shin HJ, Roh HG, Cho JM. MR imaging of glioblastoma in children: usefulness of diffusion/perfusionweighted MRI and MR spectroscopy. Pediatr Radiol 2003;33: 836 – 42. [11] Bendszus M, Warmuth-Metz M, Klein R, et al. MR spectroscopy in gliomatosis cerebri. Am J Neuroradiol 2000;21:375 – 80. [12] Kleihues P, Burger PC, Scheithauer PW. The new WHO classification of brain tumors. Brain Pathol 1993;3:255 – 68. [13] Nevin S. Gliomatosis cerebri. Brain 1938;61:170 – 91. [14] Saraf-Lavi E, Bowen BC, Pattany PM, Skiar EML, Murdoch JB, Petito CK. Proton MR spectroscopy of gliomatosis cerebri: case report of elevated myoinositol with normal choline levels. Brain 2003; 24:946 – 51. [15] Galanaud D, Chinot O, Nicoli F, Confort-Gouny S, Le Fur Y, BarrieAttarian M, et al. Use of proton magnetic resonance spectroscopy of the brain to differentiate cerebri from low-grade glioma. J Neurosurg 2003;98:269 – 76. [16] Fountas KN, Kapsalaki EZ, Vogel RI, Fezoulidis I, Robinson JS, Gotsis ED. Noninvasive histologic grading of solid astrocytomas using proton magnetic resonance spectroscopy. Stereotact Funct Neurosurg 2004;82:90 – 7. [17] Hecht BK, Turc-Carel C, Chatel M, et al. Chromosomes in gliomatosis cerebri. Genes Chromosomes Cancer 1995;14:149 – 53. [18] Blumbergs PC, Chin DF, Hallpike JF. Diffuse infiltrating astrocytoma (gliomatosis cerebri) with twenty-two-year history. Clin Exp Neurol 1983;19:94 – 101.
Magnetic resonance spectroscopy: a noninvasive diagnosis of gliomatosis cerebri Evangelia Kararizou a,*, Dimitrios Likomanosb, Konstantinos Gkiatasb, Ioannis Markoub, Nikolaos Triantafylloua, Grhgorios Kararizosb a
Department of Neurology, Eginition Hospital, Athens National University, Athens, Greece PC 11525 b Neurological Clinic, Air Force Hospital, Athens, Greece PC 11525 Received 24 September 2005; revised 15 October 2005; accepted 15 October 2005
Abstract Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of neoplastic glial cells with preservation of neuronal architecture. It can be very difficult to diagnose during life because the clinical manifestations are protean and tests are often nondiagnostic. The diagnosis of GC needs to be based on radiological, clinical and pathological criteria. We present a patient with GC, which initially presented as acute stroke attack. We discuss the usefulness of noninvasive methods, such a MR spectroscopy, in the diagnosis, grading and management of GC. D 2006 Elsevier Inc. All rights reserved. Keywords: Gliomatosis cerebri; Magnetic resonance spectroscopy
1. Introduction Gliomatosis cerebri (GC) is a rare primary brain tumor of unknown origin characterized by the proliferation of neoplastic glial cells, and this process may involve multiple brain regions [1– 4]. It can be very difficult to diagnose during life because the clinical manifestations are protean and tests are often nondiagnostic [5,6]. The diagnosis of GC needs to be based on radiological, clinical and pathological criteria [7,8]. Magnetic resonance imaging (MRI) has become the radiological method of choice in the diagnosis of GC [9]. Conventional MRI shows a diffuse signal intensity abnormality in T2-weighted and fluid-attenuated inversion recovery images with minimal or no mass effect and a lack of contrast enhancement. Magnetic resonance spectroscopy (MRS), which may be added to conventional MRI exam, provides a noninvasive biochemical assay of normal and pathological brain tissue and may help narrow the differential diagnosis in favor of a neoplastic lesion by revealing increased Cho/Cr and Cho/NA and variably decreased NA/Cr [10,11]. We present a patient with GC, which initially presented as acute stroke attack. We discuss the usefulness of 4 Corresponding author. Neurologic Clinic, Aeginition Hospital, 11528 Athens, Greece. Tel.: +30 210 7289216; fax: +30 210 7250410. E-mail address: [email protected] (E. Kararizou ). 0730-725X/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.mri.2005.10.032
noninvasive methods, such MR spectroscopy, in the diagnosis, grading and management of GC. 2. Case report A 59-year-old female patient presented with acute onset of dizziness, nausea, confusion and olfactory hallucinations. She had a history of pulmonary embolism and had been treated with anticoagulant drugs. There were no complaints of cognitive or behavioral impairments. The clinical examination revealed decreased level of consciousness and confusion. The motor strength was normal, and no sensory deficits were detected. Babinski sign was negative. With these findings and the acute onset of symptoms, the diagnosis of stroke attack was made in another institution. Afterwards, the patient was admitted in Air Force Hospital, and, immediately, a head CT scan was performed, which revealed a heterogeneous lesion in the left frontal lobe, compressing the frontal horn of the left lateral ventricle and causing significant midline shift. Indefinite components of subarachnoid hemorrhage were also observed. Cranial MRI demonstrated extensive parenchymatous lesions with the following features: (a) extensive signal changes in the left cerebral hemisphere, especially involving the white matter of the temporal lobe with a frontoparietal spreading, including basal ganglia and internal
206
E. Kararizou et al. / Magnetic Resonance Imaging 24 (2006) 205 – 207
Fig. 1. Concentrations of the spectroscopic metabolites.
capsule. (b) T2-signal abnormalities in the white matter of the right hemicerebrum, especially occitotemporally via the corpus callosum. (c) An ischemic lesion was observed in the left occitotemporal district with peripheral hemorrhagic elements. (d) Other ischemic lesions were recognised in the left side of the midbrain and in the right side of pons. (e) Cerebral edema was extended up to the cortex of the left hemisphere, where cortical sulcuses were obscured. Magnetic resonance spectroscopy of the cerebral vasculature revealed no stenosis or occlusion of either carotid or vertebrobasilar circulation. From the imaging findings (head CT scan, cranial MRI) the differential diagnosis included GC, subacute encephalitis and any systemic disease with involvement of the central nervous system. So further laboratory examinations, including extended serologic tests for systemic infectious and inflammatory diseases, connective tissue and autoimmune diseases along with cancer, were performed and the results were all normal. Interictal EEG showed high-voltage activity with a left hemispheric predominance. As mentioned above, there was a history of pulmonary embolism and treatment with anticoagulants and this was the main reason that a brain biopsy was contraindicated. Proton MRS was performed. Four NMR spectra of protons with TE = 35 and 135 ms were taken from the lesion in the left temporoparietal area and the respective area of the right hemisphere (Fig. 1). The concentration of choline (Cho), N-acetyl-aspartate (NAA), creatine (Cr), myo-inositol (MI), lactate, lipids as well as the metabolic ratios of Cho/Cr, NAA/Cr and NAA/Cho was calculated (Table 1). The concentration of Cho in the lesion is 45% higher than that of the respective healthy region of cerebral hemisphere. This finding is compatible with neoplasm (or malignancy).
The NAA concentration is quite low in the lesion area (about 65%). The presence of Cr in the lesion area indicates neoplasm of diffuse type (glioma), and the elevation of the Cho/Cr is compatible with low-grade glioma. Finally, the presence of lactic acid indicates the initiation of alteration in parts of the lesion (anaplastic astrocytoma grade III). Taking into account the neuroimaging findings (extension of the lesion to the right hemisphere, heterogeneous contrast enhancement), we found that this lesion fulfills the criteria of WHO for being characterized as GC [12]. At that time the patient had been treated with corticosteroids that resulted in significant improvement of symptoms over a period of 3 months. Although the initial symptoms of our patient included dizziness, nausea, confusion and olfactory hallucinations, no neurological sign or symptom was reported or revealed during hospitalization, despite the extent of the cerebral lesion. The last MRI, which was performed in May 2005, was reported to be unchanged. The neurological examination did not reveal any pathological findings. 3. Discussion Gliomatosis cerebri is characterized by a diffuse infiltration of neoplastic glial cells with preservation of neuronal architecture. It was first described in a case report by Nevin [13] in 1938 as a glial neoplasm with diffuse infiltration throughout the brain yet with relative preservation of underlying neuronal architecture. In the latest WHO classification GC is listed as a subgroup of neuroepithelial tumors of uncertain origin with involvement of at least two lobes without a cellular, centrally necrotic center [12].
Table 1 Area
Cho (mM/kg)
Cr (mM/kg)
NAA (mM/kg)
MI (mM/kg)
NAA/Cr
Cho/Cr
MI/Cr
Lesion 1 Lesion 2 Healthy region
3.21 3.41 2.36
6.14 6.61 7.40
3.11 3.12 8.88
6.28 6.46 7.21
0.58 0.54 1.37
1.38 1.36 0.84
0.62 0.59 0.59
E. Kararizou et al. / Magnetic Resonance Imaging 24 (2006) 205 – 207
The diagnosis of GC during life is problematic and needs to be based on radiological, clinical and pathological criteria. There are many reports of a delayed antemortem diagnosis of GC [5,6]. In our case, brain biopsy was contraindicated because of the treatment with anticoagulants. The diagnosis was based especially on the neuroimaging studies. A recent report suggests that noninvasive biochemical assay of normal and pathological brain tissue with MR spectroscopy may be helpful in diagnosing GC [10,11,14,15]. The typical MRI appearance of GC is a lesion that grows without distinct borders, diffusely infiltrating multiple brain regions. However, the changes in MR images are nonspecific and the differential diagnosis includes ischemia, multiple sclerosis, encephalitis, leukodystrophies and subacute sclerosing panencephalitis [9]. Serologic and radiology tests excluded all other conditions considered in the differential diagnosis. Magnetic resonance spectroscopy is able to distinguish between glial tumors and tumors of neuronal origin. A number of previous studies have reported elevated Cho and decreased NAA and Cr, and this spectroscopic pattern of neoplastic brain lesions has been used to differentiate and to establish prognostic parameters [10,11,14,15]. The extent of Cho/Cr and Cho/NAA increases is of great importance in the grading of gliomatosis. According to the study of Fountas et al. [16], Cho/Pcr-Cr is a very important marker determining the degree of malignancy. Magnetic resonance spectroscopy can also be used for follow-up examination. The clinical manifestations of GC are usually progressive and nonspecific, and the acute onset as stroke is rare [1– 4]. With the use of radiation therapy and chemotherapy, survival is about 5% and the natural course is quite variable, with a duration between 25 days and 22 years [17,18]. Although the initial symptoms of our patient included dizziness, nausea, confusion and olfactory hallucinations, no neurological sign or symptom was reported or revealed during hospitalization, despite the extent of the cerebral lesion. In conclusion, our report suggests that MRS is a useful noninvasive method not only for diagnosis but also for grading and prognosis of GC and especially when there are contraindications for the biopsy study.
207
References [1] Scheinker IM, Evans JP. Diffuse cerebral glio-blastosis. J Neuropathol Exp Neurol 1943;2:178 – 89. [2] Intracranial neoplasms and paraneoplastic disorders. In: Adams RD, et al, editors. Principles of neurology, 8th ed. New York7 McGrawHill; 2000. p. 673 – 733. [3] Heffner RR. Pathology of nervous system tumors. In: Bradley WC, Daroff RB, Fenichel GM, Marsden CD, editors. Neurology in clinical practice. Boston7 Butterworth-Heinemann; 1995. p. 1091 – 108. [4] Akimodo J, Nishioka H, Miki T, Haraoka J, Kado M. Clinical diagnosis of gliomatosis cerebri: report of three cases. Brain Tumor Pathol 2004;21:87 – 95. [5] Phtinen J, P77kkf E. A difficult diagnosis of gliomatosis cerebri. Neuroradiology 1996;38:444 – 8. [6] Nishioka H, Ito H, Miki T. Difficulties in the antemortem diagnosis of gliomatosis cerebri: report of a case with diffuse increase of gemistocyte-like cells, mimicking reactive gliosis. Br J Neurosurg 1996;10:103 – 7. [7] Felsberg GJ, Silver SA, Brown MT, Tien RD. Gliomatosis cerebri: radiologic–pathologic correlation. Am J Neuroradiol 1994;15: 1745 – 51. [8] Caprio-O’Donovan R, Korah I, Salazar A, Melacon D. Gliomatosis cerebri. Radiology 1996;198:831 – 5. [9] Yang S, Wetzel S, Cha S. Dynamic contrast-enhanced T2*-weighted MR imaging of gliomatosis cerebri. Am J Neuroradiol 2002;23: 350 – 5. [10] Chang YW, Yoon HK, Shin HJ, Roh HG, Cho JM. MR imaging of glioblastoma in children: usefulness of diffusion/perfusionweighted MRI and MR spectroscopy. Pediatr Radiol 2003;33: 836 – 42. [11] Bendszus M, Warmuth-Metz M, Klein R, et al. MR spectroscopy in gliomatosis cerebri. Am J Neuroradiol 2000;21:375 – 80. [12] Kleihues P, Burger PC, Scheithauer PW. The new WHO classification of brain tumors. Brain Pathol 1993;3:255 – 68. [13] Nevin S. Gliomatosis cerebri. Brain 1938;61:170 – 91. [14] Saraf-Lavi E, Bowen BC, Pattany PM, Skiar EML, Murdoch JB, Petito CK. Proton MR spectroscopy of gliomatosis cerebri: case report of elevated myoinositol with normal choline levels. Brain 2003; 24:946 – 51. [15] Galanaud D, Chinot O, Nicoli F, Confort-Gouny S, Le Fur Y, BarrieAttarian M, et al. Use of proton magnetic resonance spectroscopy of the brain to differentiate cerebri from low-grade glioma. J Neurosurg 2003;98:269 – 76. [16] Fountas KN, Kapsalaki EZ, Vogel RI, Fezoulidis I, Robinson JS, Gotsis ED. Noninvasive histologic grading of solid astrocytomas using proton magnetic resonance spectroscopy. Stereotact Funct Neurosurg 2004;82:90 – 7. [17] Hecht BK, Turc-Carel C, Chatel M, et al. Chromosomes in gliomatosis cerebri. Genes Chromosomes Cancer 1995;14:149 – 53. [18] Blumbergs PC, Chin DF, Hallpike JF. Diffuse infiltrating astrocytoma (gliomatosis cerebri) with twenty-two-year history. Clin Exp Neurol 1983;19:94 – 101.